We are engaged in the study of the immunobiology of RCC and the immune response to the tumor in patients with metastatic RCC. Our principle interest is the study of the helper T cells (CD4) infiltrating into these human tumors and their functional and phenotypic characteristics. We are also attempting to develop methodology to grow these CD4 T cells in such a way as to preserve their antigen specificity in an attempt to produce Th1 T cells by varying culture conditions. We have studied CD4+ tumor infiltrating lymphocytes obtained by culturing single cell suspensions of RCC in interleukin-2. Using our previously derived methodology to detect individual T cell reactivity we have been able to detect in one such TIL culture RCC antigen specific reactivity. This line can potentially be used to purify the RCC antigen recognized by these cells. Continuing study of MHC class I and class II expression in RCC has demonstrated that one cell line obtained from RCC a patient with sarcomatoid RCC manifested a defect in beta II microglobulin expression. Such a failure of expression of class I MHC would result in complete inability of CTL to recognize this patient's tumor. At present we are continuing studies to identify other such patients with such a defect and to determine if this might be a clinically relevant parameter in renal cell carcinoma. In a study of activation markers on the surface of CD4 T cells in RCC we have demonstrated that the CD4 cells infiltrating the tumors have activation markers and appear to have encountered antigen as opposed to the majority of CD4 T cells in the peripheral blood obtained from the same patients which do not manifest such activation markers. This suggests that RCC tumors represent an antigenic and active immunologic mileau. We are presently studying the functional capabilities of the CD4 T cells infiltrating into the tumors to determine if they manifest a Th1 or Th2 type of pattern.